Faculty Sponsor(s)
Megan Bestwick
Location
Jereld R. Nicholson Library: Grand Avenue
Subject Area
Biochemistry and Molecular Biology
Description
Mitochondria are important organelles in eukaryotic cells due to their role in metabolism. They also have their own genome (mtDNA) which encodes many of the protein subunits within the oxidative phosphorylation (OXPHOS) pathway. The remaining protein subunits are encoded in the nuclear genome, translated in the cytosol, and imported into mitochondria. Transcriptional coordination between these two genomes to produce functional OXPHOS complexes is critical to maintaining cellular homeostasis. A major control point is transcription, this process requires regulatory proteins that determine the expression of these genes. Retinoid X receptor alpha (RXRα) is a protein that has many functions in human cells and is a ligand activated nuclear receptor. It can also translocate to the mitochondria where its purpose is unknown. The goal of this project is to determine the role of RxRα as a mitochondrial transcription factor. We have expressed and purified the RXRα protein, and then also assessed its DNA binding affinity with various mtDNA sequences. We concluded RXRα binds as a dimer with space between the binding sites. Our aim is to investigate RxRα binding the mtDNA using atomic force microscopy (AFM). In doing so we will better understand the mechanisms that are involved in mtDNA transcription. If RxRα is a transcription factor, that is another protein that we can regulate to increase or decrease transcription. Being able to increase or decrease transcription in mitochondria is important as mitochondrial dysfunction causes a wide array of diseases and plays a part in aging.
Recommended Citation
Weiser, James and Bestwick, Megan, "Is Retinoid X receptor alpha a mtDNA transcription factor?" (2022). Linfield University Student Symposium: A Celebration of Scholarship and Creative Achievement. Event. Submission 32.
https://digitalcommons.linfield.edu/symposium/2022/all/32
Is Retinoid X receptor alpha a mtDNA transcription factor?
Jereld R. Nicholson Library: Grand Avenue
Mitochondria are important organelles in eukaryotic cells due to their role in metabolism. They also have their own genome (mtDNA) which encodes many of the protein subunits within the oxidative phosphorylation (OXPHOS) pathway. The remaining protein subunits are encoded in the nuclear genome, translated in the cytosol, and imported into mitochondria. Transcriptional coordination between these two genomes to produce functional OXPHOS complexes is critical to maintaining cellular homeostasis. A major control point is transcription, this process requires regulatory proteins that determine the expression of these genes. Retinoid X receptor alpha (RXRα) is a protein that has many functions in human cells and is a ligand activated nuclear receptor. It can also translocate to the mitochondria where its purpose is unknown. The goal of this project is to determine the role of RxRα as a mitochondrial transcription factor. We have expressed and purified the RXRα protein, and then also assessed its DNA binding affinity with various mtDNA sequences. We concluded RXRα binds as a dimer with space between the binding sites. Our aim is to investigate RxRα binding the mtDNA using atomic force microscopy (AFM). In doing so we will better understand the mechanisms that are involved in mtDNA transcription. If RxRα is a transcription factor, that is another protein that we can regulate to increase or decrease transcription. Being able to increase or decrease transcription in mitochondria is important as mitochondrial dysfunction causes a wide array of diseases and plays a part in aging.
